The ultimate goal of tissue engineering is to fabricate functional three-dimensional tissues and organs in order to maintain, restore, or enhance native tissue and organ function. The primary emphasis of tissue engineering is the design and fabrication of constructs for the replacement of nonfunctional tissue. Because tissue represents a highly organized interplay of cells and extracellular matrix, the fabrication of replacement tissue should mimic this spatial organization.
The classical tissue engineering approach involves the use of solid, rigid scaffolds from polyglycolic acid (PGA) and isolated cells (Langer and Vacanti, 1993). It is based on the premise that seeding cells in a bioreactor on porous biodegradable scaffolds will be sufficient to generate organs. However, cell penetration and seeding is not very effective due to several reasons. Organs usually consist of many cell types, and the need to place different cell types in specific positions is a very challenging technical problem in solid scaffold design. Rigid, solid scaffolds made from PLA are not optimal for engineering contractile tissue, such as heart and vascular tubes. The main problem with using solid scaffold seeding technology is the absence of vascularization.
Cell printers have also been developed for printing two-dimensional (2D) tissue constructs by placing solutions of cells or polymers into a specific place by the use of specially designed software. This was subsequently extended to three dimensions by the use of nontoxic, biodegradable, thermo-reversible gels, which are fluid at 20° C. and gel above 32° C. These gels are used as a sort of “paper” on which tissue structures can be printed, and cells aggregates are the “ink.” Successive layers are generated by dropping another layer of gel onto the previously printed surface. Therefore, three dimensions are obtained by stacking new sheets of “paper” on top of each prior layer. However, this technique assumes, based on the Differential Adhesion Hypothesis (DAH), that cells will sort out based on differences in the adhesive strength. For example, cell types that sort to the center of a heterocellular aggregate are assumed to generally have a stronger adhesion strength (and thus higher surface tension) than cells that sort to the outside of the aggregate. Accordingly, it is difficult to generate tissue shapes other than spheres using this approach.